Alpha-synuclein increases in rodent and human spinal cord injury and promotes inflammation and tissue loss

Autor: Anthony N. Alfredo, Evan Z. Goldstein, Andrew D. Sauerbeck, Dana M. McTigue, Alexander Marcillo, Michael D. Norenberg
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Pathology
Dopamine
animal diseases
Cell death in the nervous system
Mice
chemistry.chemical_compound
0302 clinical medicine
Spinal cord injury
Aged
80 and over
Neurons
Multidisciplinary
Cell Death
Organ Size
Middle Aged
medicine.anatomical_structure
Spinal Cord
Gene Knockdown Techniques
Knockout mouse
alpha-Synuclein
Medicine
Female
Inflammation Mediators
medicine.symptom
Signal Transduction
Adult
medicine.medical_specialty
Iron
Science
Rodentia
Inflammation
Biology
Article
Young Adult
03 medical and health sciences
Downregulation and upregulation
medicine
Animals
Humans
Spinal Cord Injuries
Aged
Alpha-synuclein
Synucleinopathies
medicine.disease
Spinal cord
Rats
nervous system diseases
Disease Models
Animal
030104 developmental biology
chemistry
nervous system
Astrocytes
Diseases of the nervous system
Neuron
Biomarkers
030217 neurology & neurosurgery
Zdroj: Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
Scientific Reports
ISSN: 2045-2322
Popis: Synucleinopathies are neurodegenerative diseases in which α-synuclein protein accumulates in neurons and glia. In these diseases, α-synuclein forms dense intracellular aggregates that are disease hallmarks and actively contribute to tissue pathology. Interestingly, many pathological mechanisms, including iron accumulation and lipid peroxidation, are shared between classical synucleinopathies such as Alzheimer’s disease, Parkinson’s disease and traumatic spinal cord injury (SCI). However, to date, no studies have determined if α-synuclein accumulation occurs after human SCI. To examine this, cross-sections from injured and non-injured human spinal cords were immunolabeled for α-synuclein. This showed robust α-synuclein accumulation in profiles resembling axons and astrocytes in tissue surrounding the injury, revealing that α-synuclein markedly aggregates in traumatically injured human spinal cords. We also detected significant iron deposition in the injury site, a known catalyst for α-synuclein aggregation. Next a rodent SCI model mimicking the histological features of human SCI revealed aggregates and structurally altered monomers of α-synuclein are present after SCI. To determine if α-synuclein exacerbates SCI pathology, α-synuclein knockout mice were tested. Compared to wild type mice, α-synuclein knockout mice had significantly more spared axons and neurons and lower pro-inflammatory mediators, macrophage accumulation, and iron deposition in the injured spinal cord. Interestingly, locomotor analysis revealed that α-synuclein may be essential for dopamine-mediated hindlimb function after SCI. Collectively, the marked upregulation and long-lasting accumulation of α-synuclein and iron suggests that SCI may fit within the family of synucleinopathies and offer new therapeutic targets for promoting neuron preservation and improving function after spinal trauma.
Databáze: OpenAIRE
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